SK8442000A3 - Hetorocyclic compounds, method for the preparation thereof, pharmaceutical composition comprising the same and their use - Google Patents

Hetorocyclic compounds, method for the preparation thereof, pharmaceutical composition comprising the same and their use Download PDF

Info

Publication number: SK8442000A3
Authority: SK; Slovakia
Prior art keywords: pyridyl; yloxy; butyl; dione; compound
Prior art date: 1997-12-05

Application number

SK844-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Andrew Baxter

David Cheshire

Thomas Mcinally

Michael Mortimore

David Cladingboel

Original Assignee

Astrazeneca Uk Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-12-05

Filing date

1998-12-01

Publication date

2001-01-18

1998-12-01 Application filed by Astrazeneca Uk Ltd filed Critical Astrazeneca Uk Ltd

2001-01-18 Publication of SK8442000A3 publication Critical patent/SK8442000A3/sk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 140
238000000034 method Methods 0.000 title claims abstract description 100
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
238000002360 preparation method Methods 0.000 title claims abstract description 9
238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
238000004519 manufacturing process Methods 0.000 claims abstract description 3
-1 Biphenyl-4-yloxy Chemical group 0.000 claims description 43
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 30
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 17
239000012453 solvate Substances 0.000 claims description 17
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 8
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
239000001301 oxygen Substances 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
SVDDJQGVOFZBNX-UHFFFAOYSA-N 2-chloroethyl carbonochloridate Chemical compound ClCCOC(Cl)=O SVDDJQGVOFZBNX-UHFFFAOYSA-N 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
RQKAJAWLEOSVNY-LJQANCHMSA-N 3-[(2r)-1-[4-(3-chloro-4-fluorophenyl)phenoxy]-4-pyridin-3-ylbutan-2-yl]-1,3-thiazolidine-2,4-dione Chemical compound C1=C(Cl)C(F)=CC=C1C(C=C1)=CC=C1OC[C@H](N1C(SCC1=O)=O)CCC1=CC=CN=C1 RQKAJAWLEOSVNY-LJQANCHMSA-N 0.000 claims description 4
XBAHGVPCQKCVQQ-OAQYLSRUSA-N 3-[(2r)-1-[4-(3-fluorophenyl)phenoxy]-4-pyridin-3-ylbutan-2-yl]-1,3-thiazolidine-2,4-dione Chemical compound FC1=CC=CC(C=2C=CC(OC[C@@H](CCC=3C=NC=CC=3)N3C(SCC3=O)=O)=CC=2)=C1 XBAHGVPCQKCVQQ-OAQYLSRUSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
125000001188 haloalkyl group Chemical group 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
GVTBLTGFYWKKSR-UHFFFAOYSA-N 1-[1-[4-(3-methoxyphenyl)phenoxy]-4-pyridin-4-ylbutan-2-yl]pyrrolidine-2,5-dione Chemical compound COC1=CC=CC(C=2C=CC(OCC(CCC=3C=CN=CC=3)N3C(CCC3=O)=O)=CC=2)=C1 GVTBLTGFYWKKSR-UHFFFAOYSA-N 0.000 claims description 3
SLEGIHLFNXPGIL-UHFFFAOYSA-N 3-[1-[4-(4-chlorophenyl)phenoxy]-4-pyridin-4-ylbutan-2-yl]-1,3-oxazolidin-2-one Chemical compound C1=CC(Cl)=CC=C1C(C=C1)=CC=C1OCC(N1C(OCC1)=O)CCC1=CC=NC=C1 SLEGIHLFNXPGIL-UHFFFAOYSA-N 0.000 claims description 3
SOKXBLLWWVPZCM-JOCHJYFZSA-N 3-[4-[(2r)-2-(2,4-dioxo-1,3-thiazolidin-3-yl)-4-pyridin-3-ylbutoxy]phenyl]benzonitrile Chemical compound O=C1CSC(=O)N1[C@@H](COC=1C=CC(=CC=1)C=1C=C(C=CC=1)C#N)CCC1=CC=CN=C1 SOKXBLLWWVPZCM-JOCHJYFZSA-N 0.000 claims description 3
DKVAJDQCPRHXSA-HSZRJFAPSA-N 3-[4-[(2r)-2-(2,5-dioxopyrrolidin-1-yl)-4-pyridin-3-ylbutoxy]phenyl]benzonitrile Chemical compound O=C1CCC(=O)N1[C@@H](COC=1C=CC(=CC=1)C=1C=C(C=CC=1)C#N)CCC1=CC=CN=C1 DKVAJDQCPRHXSA-HSZRJFAPSA-N 0.000 claims description 3
SOKXBLLWWVPZCM-QFIPXVFZSA-N 3-[4-[(2s)-2-(2,4-dioxo-1,3-thiazolidin-3-yl)-4-pyridin-3-ylbutoxy]phenyl]benzonitrile Chemical compound O=C1CSC(=O)N1[C@H](COC=1C=CC(=CC=1)C=1C=C(C=CC=1)C#N)CCC1=CC=CN=C1 SOKXBLLWWVPZCM-QFIPXVFZSA-N 0.000 claims description 3
CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 claims description 3
YKMPVOXAMQJSAR-NRFANRHFSA-N 5-[4-[(2s)-2-(2,4-dioxo-1,3-thiazolidin-3-yl)-4-pyridin-3-ylbutoxy]phenyl]-2-fluorobenzonitrile Chemical compound C1=C(C#N)C(F)=CC=C1C(C=C1)=CC=C1OC[C@@H](N1C(SCC1=O)=O)CCC1=CC=CN=C1 YKMPVOXAMQJSAR-NRFANRHFSA-N 0.000 claims description 3
SUDYQCRLMSFLSC-UHFFFAOYSA-N Fc1ccc(cc1)-c1ccc(OCC(CCc2ccncc2)N2C(=O)CSC2=O)cc1 Chemical compound Fc1ccc(cc1)-c1ccc(OCC(CCc2ccncc2)N2C(=O)CSC2=O)cc1 SUDYQCRLMSFLSC-UHFFFAOYSA-N 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
HAOHUIPHEIQXOP-NRFANRHFSA-N Nc1cccc(c1)-c1ccc(OC[C@H](CCc2ccncc2)N2C(=O)CSC2=O)cc1 Chemical compound Nc1cccc(c1)-c1ccc(OC[C@H](CCc2ccncc2)N2C(=O)CSC2=O)cc1 HAOHUIPHEIQXOP-NRFANRHFSA-N 0.000 claims description 3
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 2
NRDKFCWQKJPTEO-UHFFFAOYSA-N 1-[1-[4-(3-nitrophenyl)phenoxy]-4-pyridin-4-ylbutan-2-yl]piperidin-2-one Chemical compound [O-][N+](=O)C1=CC=CC(C=2C=CC(OCC(CCC=3C=CN=CC=3)N3C(CCCC3)=O)=CC=2)=C1 NRDKFCWQKJPTEO-UHFFFAOYSA-N 0.000 claims description 2
STKHWLHESIEASL-UHFFFAOYSA-N 3-[1-[4-(3-nitrophenyl)phenoxy]-4-pyridin-4-ylbutan-2-yl]-1,3-oxazinan-2-one Chemical compound [O-][N+](=O)C1=CC=CC(C=2C=CC(OCC(CCC=3C=CN=CC=3)N3C(OCCC3)=O)=CC=2)=C1 STKHWLHESIEASL-UHFFFAOYSA-N 0.000 claims description 2
VQEHBLGYANQWEA-UHFFFAOYSA-N 3-[1-[4-(3-nitrophenyl)phenoxy]-4-pyridin-4-ylbutan-2-yl]-1,3-thiazolidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC(C=2C=CC(OCC(CCC=3C=CN=CC=3)N3C(SCC3=O)=O)=CC=2)=C1 VQEHBLGYANQWEA-UHFFFAOYSA-N 0.000 claims description 2
LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 claims description 2
VHSLDJFCQNKIDO-UHFFFAOYSA-N COc1cccc(c1)-c1ccc(OCC(CCc2cccnc2)N2C(=O)CCC2=O)cc1 Chemical compound COc1cccc(c1)-c1ccc(OCC(CCc2cccnc2)N2C(=O)CCC2=O)cc1 VHSLDJFCQNKIDO-UHFFFAOYSA-N 0.000 claims description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
NLFNIAUXHRTPJG-UHFFFAOYSA-N Clc1cccc(c1)-c1ccc(OCC(CCc2cccnc2)N2C(=O)CCC2=O)cc1 Chemical compound Clc1cccc(c1)-c1ccc(OCC(CCc2cccnc2)N2C(=O)CCC2=O)cc1 NLFNIAUXHRTPJG-UHFFFAOYSA-N 0.000 claims description 2
DYJJGMCDWDOODS-UHFFFAOYSA-N Fc1cccc(c1)-c1ccc(OCC(CCc2cccnc2)N2C(=O)CCC2=O)cc1 Chemical compound Fc1cccc(c1)-c1ccc(OCC(CCc2cccnc2)N2C(=O)CCC2=O)cc1 DYJJGMCDWDOODS-UHFFFAOYSA-N 0.000 claims description 2
206010062016 Immunosuppression Diseases 0.000 claims description 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
238000006243 chemical reaction Methods 0.000 claims description 2
230000001506 immunosuppresive effect Effects 0.000 claims description 2
239000000654 additive Substances 0.000 claims 2
230000000996 additive effect Effects 0.000 claims 2
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
DNFYUGQOSDLSNQ-UHFFFAOYSA-N 1-[1-[4-(3-nitrophenyl)phenoxy]-4-pyridin-4-ylbutan-2-yl]pyrrolidin-2-one Chemical compound [O-][N+](=O)C1=CC=CC(C=2C=CC(OCC(CCC=3C=CN=CC=3)N3C(CCC3)=O)=CC=2)=C1 DNFYUGQOSDLSNQ-UHFFFAOYSA-N 0.000 claims 1
IEEZJIBNKVIUBD-UHFFFAOYSA-N 1-phenyl-3-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=CC(C=2C=CC=CC=2)=C1 IEEZJIBNKVIUBD-UHFFFAOYSA-N 0.000 claims 1
HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 claims 1
150000001721 carbon Chemical group 0.000 claims 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
125000004434 sulfur atom Chemical group 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
239000000243 solution Substances 0.000 description 57
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
238000005481 NMR spectroscopy Methods 0.000 description 44
239000007787 solid Substances 0.000 description 37
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
239000000203 mixture Substances 0.000 description 25
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 22
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
239000003921 oil Substances 0.000 description 15
235000019198 oils Nutrition 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
238000002844 melting Methods 0.000 description 13
230000008018 melting Effects 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 12
238000000746 purification Methods 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
229960002317 succinimide Drugs 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 10
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 10
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 10
238000010626 work up procedure Methods 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
210000004027 cell Anatomy 0.000 description 8
239000000284 extract Substances 0.000 description 8
238000010898 silica gel chromatography Methods 0.000 description 8
102100037602 P2X purinoceptor 7 Human genes 0.000 description 7
101710189965 P2X purinoceptor 7 Proteins 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
239000000725 suspension Substances 0.000 description 7
ZMDQVFXSNXQAHC-UHFFFAOYSA-N 1-(4-bromophenoxy)-4-pyridin-4-ylbutan-2-ol Chemical compound C=1C=C(Br)C=CC=1OCC(O)CCC1=CC=NC=C1 ZMDQVFXSNXQAHC-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 6
239000005695 Ammonium acetate Substances 0.000 description 6
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
235000019257 ammonium acetate Nutrition 0.000 description 6
229940043376 ammonium acetate Drugs 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
239000006260 foam Substances 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
239000002245 particle Substances 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
239000002904 solvent Substances 0.000 description 6
239000003643 water by type Substances 0.000 description 6
BURJIEWNHIKROD-FWDYTFEUSA-N [[(2r,3r,4r,5s)-5-(6-aminopurin-9-yl)-4,5-dibenzoyl-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C([C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@]1(N1C=2N=CN=C(C=2N=C1)N)C(=O)C=1C=CC=CC=1)C1=CC=CC=C1 BURJIEWNHIKROD-FWDYTFEUSA-N 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
238000010828 elution Methods 0.000 description 5
239000010410 layer Substances 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
238000010992 reflux Methods 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
239000012267 brine Substances 0.000 description 4
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
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238000009835 boiling Methods 0.000 description 1
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229910052794 bromium Inorganic materials 0.000 description 1
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LFTJONYSYLABPQ-OAQYLSRUSA-N n-[3-[4-[(2r)-2-hydroxy-4-pyridin-3-ylbutoxy]phenyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(C=2C=CC(OC[C@H](O)CCC=3C=NC=CC=3)=CC=2)=C1 LFTJONYSYLABPQ-OAQYLSRUSA-N 0.000 description 1
UVFWGWMMSVQZLI-QFIPXVFZSA-N n-[3-[4-[(2s)-2-(2,4-dioxo-1,3-thiazolidin-3-yl)-4-pyridin-3-ylbutoxy]phenyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(C=2C=CC(OC[C@H](CCC=3C=NC=CC=3)N3C(SCC3=O)=O)=CC=2)=C1 UVFWGWMMSVQZLI-QFIPXVFZSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
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239000012044 organic layer Substances 0.000 description 1
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238000004634 pharmacological analysis method Methods 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000004033 plastic Substances 0.000 description 1
239000011148 porous material Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000012256 powdered iron Substances 0.000 description 1
NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 1
235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
239000011589 pyridoxal 5'-phosphate Substances 0.000 description 1
229960001327 pyridoxal phosphate Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
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239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
208000027185 varicose disease Diseases 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Transplantation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK844-2000A 1997-12-05 1998-12-01 Hetorocyclic compounds, method for the preparation thereof, pharmaceutical composition comprising the same and their use SK8442000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9704546A SE9704546D0 (sv)	1997-12-05	1997-12-05	Novel compounds
PCT/SE1998/002190 WO1999029686A1 (en)	1997-12-05	1998-12-01	Novel compounds

Publications (1)

Publication Number	Publication Date
SK8442000A3 true SK8442000A3 (en)	2001-01-18

Family

ID=20409283

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK844-2000A SK8442000A3 (en)	1997-12-05	1998-12-01	Hetorocyclic compounds, method for the preparation thereof, pharmaceutical composition comprising the same and their use

Country Status (16)

Country	Link
EP (1)	EP1037889A1 (no)
JP (1)	JP2001525406A (no)
KR (1)	KR20010032800A (no)
CN (1)	CN1284074A (no)
AU (1)	AU1791599A (no)
BR (1)	BR9813378A (no)
CA (1)	CA2312357A1 (no)
EE (1)	EE200000321A (no)
HU (1)	HUP0100731A3 (no)
IL (1)	IL136368A0 (no)
NO (1)	NO20002787L (no)
PL (1)	PL340837A1 (no)
SE (1)	SE9704546D0 (no)
SK (1)	SK8442000A3 (no)
TR (1)	TR200001544T2 (no)
WO (1)	WO1999029686A1 (no)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE9901875D0 (sv) *	1999-05-25	1999-05-25	Astra Pharma Prod	Novel compounds
SE9904505D0 (sv)	1999-12-09	1999-12-09	Astra Pharma Prod	Novel compounds
SE9904652D0 (sv) *	1999-12-17	1999-12-17	Astra Pharma Prod	Novel Compounds
TWI258462B (en)	1999-12-17	2006-07-21	Astrazeneca Ab	Adamantane derivative compounds, process for preparing the same and pharmaceutical composition comprising the same
JP2002330787A (ja) *	2000-10-21	2002-11-19	Astrazeneca Ab	化学物質
WO2003042190A1 (en)	2001-11-12	2003-05-22	Pfizer Products Inc.	N-alkyl-adamantyl derivatives as p2x7-receptor antagonists
PA8557501A1 (es)	2001-11-12	2003-06-30	Pfizer Prod Inc	Benzamida, heteroarilamida y amidas inversas
PA8591801A1 (es)	2002-12-31	2004-07-26	Pfizer Prod Inc	Inhibidores benzamidicos del receptor p2x7.
US7071223B1 (en)	2002-12-31	2006-07-04	Pfizer, Inc.	Benzamide inhibitors of the P2X7 receptor
ES2281801T3 (es)	2003-05-12	2007-10-01	Pfizer Products Inc.	Inhibidores benzamida del receptor p2x7.
GB0324498D0 (en)	2003-07-21	2003-11-26	Aventis Pharma Inc	Heterocyclic compounds as P2X7 ion channel blockers
BRPI0512781A (pt)	2004-06-29	2008-04-08	Pfizer Prod Inc	método para preparação de derivados de 5-{4-(2-hidroxi-propil)-3,5-dioxo-4,5-diidro-3h-[1,2,4]tria zin-2-il}-benzamida através da desproteção dos precursores de protetores de hidroxila
CA2645551C (en)	2006-03-16	2016-06-28	Renovis, Inc.	Bicycloheteroaryl compounds as p2x7 modulators and uses thereof
DK2001474T3 (en)	2006-03-16	2016-05-09	Second Genome Inc	BICYCLOHETEROARYL COMPOUNDS AS P2X7 MODULATORS AND APPLICATIONS THEREOF
TWI464148B (zh)	2006-03-16	2014-12-11	Evotec Us Inc	作為ｐ２ｘ7調節劑之雙環雜芳基化合物與其用途
TW200813018A (en)	2006-06-09	2008-03-16	Astrazeneca Ab	Novel compounds
GB0613473D0 (en) *	2006-07-06	2006-08-16	Glaxo Group Ltd	Novel compounds
EA016076B1 (ru) *	2006-07-06	2012-01-30	Глэксо Груп Лимитед	Замещенные n-фенилметил-5-оксопролин-2-амиды в качестве антагонистов р2х7-рецептора и способы их применения
CN101686680B (zh)	2007-03-09	2015-12-09	伊沃泰克美国股份有限公司	作为p2x7调节剂的双环杂芳基化合物及其用途
JP2010522711A (ja) *	2007-03-28	2010-07-08	グラクソグループリミテッド	Ｐ２ｘ７調節因子としてのピペリジノンカルボキサミド誘導体
EP2139875A2 (en) *	2007-03-29	2010-01-06	Glaxo Group Limited	Oxazolidine and morpholine carboxamide derivatives as p2x7 modulators
MX2009010759A (es)	2007-04-03	2009-10-28	Glaxo Group Ltd	Derivados de carboxamida imidazolidina como modulares de p2x7.
US8119661B2 (en)	2007-09-11	2012-02-21	Astrazeneca Ab	Piperidine derivatives and their use as muscarinic receptor modulators
GB0803729D0 (en) *	2008-02-29	2008-04-09	Ge Healthcare Ltd	Imaging the central nervous system
NZ587799A (en)	2008-03-25	2012-06-29	Affectis Pharmaceuticals Ag	Novel p2x7r antagonists and their use
ES2380908T3 (es)	2009-04-14	2012-05-21	Affectis Pharmaceuticals Ag	Antagonistas de p2x7r novedosos y su uso
EP2322149A1 (en)	2009-11-03	2011-05-18	Universidad del Pais Vasco	Methods and compositions for the treatment of ischemia
JP2013526496A (ja)	2010-05-14	2013-06-24	アフェクティスファーマシューティカルズアーゲー	Ｐ２ｘ７ｒ拮抗剤の新規調製方法
WO2012110190A1 (en)	2011-02-17	2012-08-23	Affectis Pharmaceuticals Ag	Novel p2x7r antagonists and their use
WO2012163456A1 (en)	2011-05-27	2012-12-06	Affectis Pharmaceuticals Ag	Novel p2x7r antagonists and their use
WO2012163792A1 (en)	2011-05-27	2012-12-06	Affectis Pharmaceuticals Ag	Novel p2x7r antagonists and their use
AU2018372136B2 (en)	2017-11-21	2022-01-27	Solventum Intellectual Properties Company	Oral plant-based-oil-in-water emulsions and methods of use
US11324681B2 (en)	2017-12-20	2022-05-10	3M Innovative Properties Company	Oral compositions and methods of use
EP3727336A1 (en)	2017-12-20	2020-10-28	3M Innovative Properties Company	Oral compositions and methods of use
WO2020136606A1 (en)	2018-12-29	2020-07-02	3M Innovative Properties Company	Oral articles and methods of use
WO2020136620A1 (en)	2018-12-29	2020-07-02	3M Innovative Properties Company	Oral articles and methods of use

1997
- 1997-12-05 SE SE9704546A patent/SE9704546D0/xx unknown
1998
- 1998-12-01 SK SK844-2000A patent/SK8442000A3/sk unknown
- 1998-12-01 PL PL98340837A patent/PL340837A1/xx unknown
- 1998-12-01 KR KR1020007006117A patent/KR20010032800A/ko not_active Withdrawn
- 1998-12-01 EE EEP200000321A patent/EE200000321A/xx unknown
- 1998-12-01 IL IL13636898A patent/IL136368A0/xx unknown
- 1998-12-01 CA CA002312357A patent/CA2312357A1/en not_active Abandoned
- 1998-12-01 WO PCT/SE1998/002190 patent/WO1999029686A1/en not_active Ceased
- 1998-12-01 EP EP98962753A patent/EP1037889A1/en not_active Withdrawn
- 1998-12-01 BR BR9813378-0A patent/BR9813378A/pt not_active Application Discontinuation
- 1998-12-01 TR TR2000/01544T patent/TR200001544T2/xx unknown
- 1998-12-01 JP JP2000524280A patent/JP2001525406A/ja not_active Withdrawn
- 1998-12-01 AU AU17915/99A patent/AU1791599A/en not_active Abandoned
- 1998-12-01 HU HU0100731A patent/HUP0100731A3/hu unknown
- 1998-12-01 CN CN98813490A patent/CN1284074A/zh active Pending
2000
- 2000-05-31 NO NO20002787A patent/NO20002787L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
NO20002787D0 (no)	2000-05-31
SE9704546D0 (sv)	1997-12-05
JP2001525406A (ja)	2001-12-11
BR9813378A (pt)	2000-10-10
WO1999029686A1 (en)	1999-06-17
EE200000321A (et)	2001-08-15
KR20010032800A (ko)	2001-04-25
PL340837A1 (en)	2001-02-26
EP1037889A1 (en)	2000-09-27
AU1791599A (en)	1999-06-28
NO20002787L (no)	2000-08-01
CA2312357A1 (en)	1999-06-17
TR200001544T2 (tr)	2000-11-21
IL136368A0 (en)	2001-06-14
CN1284074A (zh)	2001-02-14
HUP0100731A3 (en)	2002-08-28
HUP0100731A2 (hu)	2002-05-29

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